Processes for synthesizing racemic 3-quinuclidinol derivatives are widely known according to e.g. Zhur. Obshchi. Khim., 30, 163-71 (1960), Helv. 40, 2107-85 (1957), and J. Am. Chem. Soc. 74, 2215-8 (1952).
On the other hand, processes for synthesizing optically active 3-quinuclidinol derivatives are known as described in e.g. Acta. Pharm. Suec., 16, 281-3 (1979), U.S. Pat. No. 3,997,543, Life sic. 21, 1293-1302 (1977) and U.S. Pat. No. 5,215,918.
The process described in Acta. Pharm. Suec., 16, 281-3 (1979) is a process in which optically active 3-quinuclidinol derivatives are derived by a preferential crystallization method using optically active tartaric acid as a resolution agent, and this prior art process requires the cumbersome procedure that e.g. recrystallization should be repeated several or more times to raise optical purity.
Further, the processes described in U.S. Pat. No. 3,997,543, Life sic. 21, 1293-1302 (1977) and U.S. Pat. No. 5,215,918 report processes for obtaining optically active 3-quinuclidinol derivatives by asymmetrically hydrolyzing lower fatty esters of 3-quinuclidinol with an enzyme. However, the enzyme used in U.S. Pat. No. 3,997,543 and Life sic. 21, 1293-1302 (1977) is a butyryl choline esterase only, and the enzyme used in U.S. Pat. No. 5,215,918 is an only specific enzyme (subtilisin) produced by the genus Bacillus, and thus the type of enzyme used in any of these literatures is limited so these cannot be said to be general processes. There are still not known any other processes for producing optically active 3-quinuclidinol derivatives by means of general enzymes.
Accordingly, the useful process for synthesizing optically active 3-quinuclidinol derivatives, provided by the present invention, has been desired.